Search

Your search keyword '"Appert, Alex"' showing total 35 results
Start Over Author "Appert, Alex"
35 results on '"Appert, Alex"'

1. The histone chaperone SPT2 regulates chromatin structure and function in Metazoa

Author

Saredi, Giulia, Carelli, Francesco N., Rolland, Stéphane G. M., Furlan, Giulia, Piquet, Sandra, Appert, Alex, Sanchez-Pulido, Luis, Price, Jonathan L., Alcon, Pablo, Lampersberger, Lisa, Déclais, Anne-Cécile, Ramakrishna, Navin B., Toth, Rachel, Macartney, Thomas, Alabert, Constance, Ponting, Chris P., Polo, Sophie E., Miska, Eric A., Gartner, Anton, Ahringer, Julie, and Rouse, John

Published
2024
Full Text
View/download PDF

2. The DREAM complex promotes gene body H2A.Z for target repression

Author

Latorre, Isabel, Chesney, Michael A, Garrigues, Jacob M, Stempor, Przemyslaw, Appert, Alex, Francesconi, Mirko, Strome, Susan, and Ahringer, Julie

Subjects
Biochemistry and Cell Biology, Biological Sciences, Biotechnology, Genetics, Animals, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Gene Expression Regulation, Developmental, Genes, cdc, Histones, Mutation, Protein Binding, Transcriptome, C. elegans, H2A.Z, Retinoblastoma/DREAM, transcriptional repression, Medical and Health Sciences, Psychology and Cognitive Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences, Psychology
Abstract

The DREAM (DP, Retinoblastoma [Rb]-like, E2F, and MuvB) complex controls cellular quiescence by repressing cell cycle genes, but its mechanism of action is poorly understood. Here we show that Caenorhabditis elegans DREAM targets have an unusual pattern of high gene body HTZ-1/H2A.Z. In mutants of lin-35, the sole p130/Rb-like gene in C. elegans, DREAM targets have reduced gene body HTZ-1/H2A.Z and increased expression. Consistent with a repressive role for gene body H2A.Z, many DREAM targets are up-regulated in htz-1/H2A.Z mutants. Our results indicate that the DREAM complex facilitates high gene body HTZ-1/H2A.Z, which plays a role in target gene repression.

Published
2015

3. Comparative analysis of metazoan chromatin organization

Author

Ho, Joshua WK, Jung, Youngsook L, Liu, Tao, Alver, Burak H, Lee, Soohyun, Ikegami, Kohta, Sohn, Kyung-Ah, Minoda, Aki, Tolstorukov, Michael Y, Appert, Alex, Parker, Stephen CJ, Gu, Tingting, Kundaje, Anshul, Riddle, Nicole C, Bishop, Eric, Egelhofer, Thea A, Hu, Sheng'en Shawn, Alekseyenko, Artyom A, Rechtsteiner, Andreas, Asker, Dalal, Belsky, Jason A, Bowman, Sarah K, Chen, Q Brent, Chen, Ron A-J, Day, Daniel S, Dong, Yan, Dose, Andrea C, Duan, Xikun, Epstein, Charles B, Ercan, Sevinc, Feingold, Elise A, Ferrari, Francesco, Garrigues, Jacob M, Gehlenborg, Nils, Good, Peter J, Haseley, Psalm, He, Daniel, Herrmann, Moritz, Hoffman, Michael M, Jeffers, Tess E, Kharchenko, Peter V, Kolasinska-Zwierz, Paulina, Kotwaliwale, Chitra V, Kumar, Nischay, Langley, Sasha A, Larschan, Erica N, Latorre, Isabel, Libbrecht, Maxwell W, Lin, Xueqiu, Park, Richard, Pazin, Michael J, Pham, Hoang N, Plachetka, Annette, Qin, Bo, Schwartz, Yuri B, Shoresh, Noam, Stempor, Przemyslaw, Vielle, Anne, Wang, Chengyang, Whittle, Christina M, Xue, Huiling, Kingston, Robert E, Kim, Ju Han, Bernstein, Bradley E, Dernburg, Abby F, Pirrotta, Vincenzo, Kuroda, Mitzi I, Noble, William S, Tullius, Thomas D, Kellis, Manolis, MacAlpine, David M, Strome, Susan, Elgin, Sarah CR, Liu, Xiaole Shirley, Lieb, Jason D, Ahringer, Julie, Karpen, Gary H, and Park, Peter J

Subjects
Biochemistry and Cell Biology, Biological Sciences, Immunization, Human Genome, Genetics, 1.1 Normal biological development and functioning, Underpinning research, Generic health relevance, Animals, Caenorhabditis elegans, Cell Line, Centromere, Chromatin, Chromatin Assembly and Disassembly, DNA Replication, Drosophila melanogaster, Enhancer Elements, Genetic, Epigenesis, Genetic, Heterochromatin, Histones, Humans, Molecular Sequence Annotation, Nuclear Lamina, Nucleosomes, Promoter Regions, Genetic, Species Specificity, General Science & Technology
Abstract

Genome function is dynamically regulated in part by chromatin, which consists of the histones, non-histone proteins and RNA molecules that package DNA. Studies in Caenorhabditis elegans and Drosophila melanogaster have contributed substantially to our understanding of molecular mechanisms of genome function in humans, and have revealed conservation of chromatin components and mechanisms. Nevertheless, the three organisms have markedly different genome sizes, chromosome architecture and gene organization. On human and fly chromosomes, for example, pericentric heterochromatin flanks single centromeres, whereas worm chromosomes have dispersed heterochromatin-like regions enriched in the distal chromosomal 'arms', and centromeres distributed along their lengths. To systematically investigate chromatin organization and associated gene regulation across species, we generated and analysed a large collection of genome-wide chromatin data sets from cell lines and developmental stages in worm, fly and human. Here we present over 800 new data sets from our ENCODE and modENCODE consortia, bringing the total to over 1,400. Comparison of combinatorial patterns of histone modifications, nuclear lamina-associated domains, organization of large-scale topological domains, chromatin environment at promoters and enhancers, nucleosome positioning, and DNA replication patterns reveals many conserved features of chromatin organization among the three organisms. We also find notable differences in the composition and locations of repressive chromatin. These data sets and analyses provide a rich resource for comparative and species-specific investigations of chromatin composition, organization and function.

Published
2014

4. H4K20me1 contributes to downregulation of X-linked genes for C. elegans dosage compensation.

Author

Vielle, Anne, Lang, Jackie, Dong, Yan, Ercan, Sevinc, Kotwaliwale, Chitra, Rechtsteiner, Andreas, Appert, Alex, Chen, Q Brent, Dose, Andrea, Egelhofer, Thea, Kimura, Hiroshi, Stempor, Przemyslaw, Dernburg, Abby, Lieb, Jason D, Strome, Susan, and Ahringer, Julie

Subjects
X Chromosome, Chromatin, Animals, Caenorhabditis elegans, Methyltransferases, Histone-Lysine N-Methyltransferase, Caenorhabditis elegans Proteins, Histones, Gene Expression Regulation, Developmental, RNA Interference, Methylation, Dosage Compensation, Genetic, Male, Genes, X-Linked, Disorders of Sex Development, Dosage Compensation, Genetic, Gene Expression Regulation, Developmental, Genes, X-Linked, Genetics, Developmental Biology
Abstract

The Caenorhabditis elegans dosage compensation complex (DCC) equalizes X-chromosome gene dosage between XO males and XX hermaphrodites by two-fold repression of X-linked gene expression in hermaphrodites. The DCC localizes to the X chromosomes in hermaphrodites but not in males, and some subunits form a complex homologous to condensin. The mechanism by which the DCC downregulates gene expression remains unclear. Here we show that the DCC controls the methylation state of lysine 20 of histone H4, leading to higher H4K20me1 and lower H4K20me3 levels on the X chromosomes of XX hermaphrodites relative to autosomes. We identify the PR-SET7 ortholog SET-1 and the Suv4-20 ortholog SET-4 as the major histone methyltransferases for monomethylation and di/trimethylation of H4K20, respectively, and provide evidence that X-chromosome enrichment of H4K20me1 involves inhibition of SET-4 activity on the X. RNAi knockdown of set-1 results in synthetic lethality with dosage compensation mutants and upregulation of X-linked gene expression, supporting a model whereby H4K20me1 functions with the condensin-like C. elegans DCC to repress transcription of X-linked genes. H4K20me1 is important for mitotic chromosome condensation in mammals, suggesting that increased H4K20me1 on the X may restrict access of the transcription machinery to X-linked genes via chromatin compaction.

Published
2012

5. Data from A20, ABIN-1/2, and CARD11 Mutations and Their Prognostic Value in Gastrointestinal Diffuse Large B-Cell Lymphoma

Author

Dong, Gehong, primary, Chanudet, Estelle, primary, Zeng, Naiyan, primary, Appert, Alex, primary, Chen, Yun-Wen, primary, Au, Wing-Yan, primary, Hamoudi, Rifat A., primary, Watkins, A. James, primary, Ye, Hongtao, primary, Liu, Hongxiang, primary, Gao, Zifen, primary, Chuang, Shih-Sung, primary, Srivastava, Gopesh, primary, and Du, Ming-Qing, primary

Published
2023
Full Text
View/download PDF

6. Supplementary Data from A20, ABIN-1/2, and CARD11 Mutations and Their Prognostic Value in Gastrointestinal Diffuse Large B-Cell Lymphoma

Author

Dong, Gehong, primary, Chanudet, Estelle, primary, Zeng, Naiyan, primary, Appert, Alex, primary, Chen, Yun-Wen, primary, Au, Wing-Yan, primary, Hamoudi, Rifat A., primary, Watkins, A. James, primary, Ye, Hongtao, primary, Liu, Hongxiang, primary, Gao, Zifen, primary, Chuang, Shih-Sung, primary, Srivastava, Gopesh, primary, and Du, Ming-Qing, primary

Published
2023
Full Text
View/download PDF

12. The histone chaperone activity of SPT2 controls chromatin structure and function in Metazoa

Author

Saredi, Giulia, primary, Carelli, Francesco N., additional, Furlan, Giulia, additional, Rolland, Stephane, additional, Piquet, Sandra, additional, Appert, Alex, additional, Sanchez-Pulido, Luis, additional, Price, Jonathan L., additional, Alcon, Pablo, additional, Lampersberger, Lisa, additional, Déclais, Anne-Cécile, additional, Ramakrishna, Navin B., additional, Toth, Rachel, additional, Ponting, Chris P., additional, Polo, Sophie E., additional, Miska, Eric A., additional, Ahringer, Julie, additional, Gartner, Anton, additional, and Rouse, John, additional

Published
2023
Full Text
View/download PDF

15. DREAM represses distinct targets by cooperating with different THAP domain proteins

Author

Gal, Csenge, Carelli, Francesco Nicola, Appert, Alex, Cerrato, Chiara, Huang, Ni, Dong, Yan, Murphy, Jane, Ahringer, Julie, Ahringer, Julie [0000-0002-7074-4051], and Apollo - University of Cambridge Repository

Subjects
FOS: Biological sciences, 1.1 Normal biological development and functioning, Genetics, 1 Underpinning research, Generic health relevance, 3101 Biochemistry and Cell Biology, humanities, psychological phenomena and processes, 31 Biological Sciences
Abstract

The DREAM (DP, Retinoblastoma [Rb]-like, E2F, and MuvB) complex controls cellular quiescence by repressing cell cycle and other genes, but its mechanism of action is unclear. Here we demonstrate that two C. elegans THAP domain proteins, LIN-15B and LIN-36, co-localize with DREAM and function by different mechanisms for repression of distinct sets of targets. LIN-36 represses classical cell cycle targets by promoting DREAM binding and gene body enrichment of H2A.Z, and we find that DREAM subunit EFL-1/E2F is specific for LIN-36 targets. In contrast, LIN-15B represses germline specific targets in the soma by facilitating H3K9me2 promoter marking. We further find that LIN-36 and LIN-15B differently regulate DREAM binding. In humans, THAP proteins have been implicated in cell cycle regulation by poorly understood mechanisms. We propose that THAP domain proteins are key mediators of Rb/DREAM function.

Published
2022
Full Text
View/download PDF

18. The Caenorhabditis elegans homolog of the Evi1 proto-oncogene, egl-43, coordinates G1 cell cycle arrest with pro-invasive gene expression during anchor cell invasion

Author

Deng, Ting, Stempor, Przemyslaw, Appert, Alex, Daube, Michael, Ahringer, Julie, Hajnal, Alex, Lattmann, Evelyn, Deng, Ting [0000-0002-4820-8535], Stempor, Przemyslaw [0000-0002-9464-7475], Ahringer, Julie [0000-0002-7074-4051], Hajnal, Alex [0000-0002-4098-3721], Lattmann, Evelyn [0000-0002-9793-2554], Apollo - University of Cambridge Repository, University of Zurich, and Hajnal, Alex

Subjects
Life Cycles, Nematoda, Gene Expression, QH426-470, Proto-Oncogene Mas, Biochemistry, Basement Membrane, RNA interference, Larvae, Cell Signaling, 1306 Cancer Research, Cell Cycle and Cell Division, Notch Signaling, Receptors, Notch, Eukaryota, Cell Differentiation, Animal Models, 10124 Institute of Molecular Life Sciences, Nucleic acids, Genetic interference, Experimental Organism Systems, Cell Processes, Epigenetics, Proto-Oncogene Proteins c-fos, Signal Transduction, Research Article, 2716 Genetics (clinical), animal structures, Research and Analysis Methods, Model Organisms, 1311 Genetics, Proto-Oncogenes, DNA-binding proteins, 1312 Molecular Biology, Genetics, Animals, Gene Regulation, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Cell Proliferation, Biology and life sciences, fungi, Organisms, Proteins, Cell Cycle Checkpoints, Cell Biology, G1 Phase Cell Cycle Checkpoints, Invertebrates, MDS1 and EVI1 Complex Locus Protein, Regulatory Proteins, 1105 Ecology, Evolution, Behavior and Systematics, Animal Studies, Caenorhabditis, 570 Life sciences, biology, RNA, Transcription Factors, Developmental Biology
Abstract

Cell invasion allows cells to migrate across compartment boundaries formed by basement membranes. Aberrant cell invasion is a first step during the formation of metastases by malignant cancer cells. Anchor cell (AC) invasion in C. elegans is an excellent in vivo model to study the regulation of cell invasion during development. Here, we have examined the function of egl-43, the homolog of the human Evi1 proto-oncogene (also called MECOM), in the invading AC. egl-43 plays a dual role in this process, firstly by imposing a G1 cell cycle arrest to prevent AC proliferation, and secondly, by activating pro-invasive gene expression. We have identified the AP-1 transcription factor fos-1 and the Notch homolog lin-12 as critical egl-43 targets. A positive feedback loop between fos-1 and egl-43 induces pro-invasive gene expression in the AC, while repression of lin-12 Notch expression by egl-43 ensures the G1 cell cycle arrest necessary for invasion. Reducing lin-12 levels in egl-43 depleted animals restored the G1 arrest, while hyperactivation of lin-12 signaling in the differentiated AC was sufficient to induce proliferation. Taken together, our data have identified egl-43 Evi1 as an important factor coordinating cell invasion with cell cycle arrest., PLoS Genetics, 16 (3), ISSN:1553-7390, ISSN:1553-7404

Published
2020
Full Text
View/download PDF

20. The Caenorhabditis elegans homolog of the Evi1 proto-oncogene, egl-43, coordinates G1 cell cycle arrest with pro-invasive gene expression during anchor cell invasion

Author

Deng, Ting; https://orcid.org/0000-0002-4820-8535, Stempor, Przemyslaw; https://orcid.org/0000-0002-9464-7475, Appert, Alex, Daube, Michael, Ahringer, Julie; https://orcid.org/0000-0002-7074-4051, Hajnal, Alex; https://orcid.org/0000-0002-4098-3721, Lattmann, Evelyn; https://orcid.org/0000-0002-9793-2554, Deng, Ting; https://orcid.org/0000-0002-4820-8535, Stempor, Przemyslaw; https://orcid.org/0000-0002-9464-7475, Appert, Alex, Daube, Michael, Ahringer, Julie; https://orcid.org/0000-0002-7074-4051, Hajnal, Alex; https://orcid.org/0000-0002-4098-3721, and Lattmann, Evelyn; https://orcid.org/0000-0002-9793-2554

Abstract

Cell invasion allows cells to migrate across compartment boundaries formed by basement membranes. Aberrant cell invasion is a first step during the formation of metastases by malignant cancer cells. Anchor cell (AC) invasion in C. elegans is an excellent in vivo model to study the regulation of cell invasion during development. Here, we have examined the function of egl-43, the homolog of the human Evi1 proto-oncogene (also called MECOM), in the invading AC. egl-43 plays a dual role in this process, firstly by imposing a G1 cell cycle arrest to prevent AC proliferation, and secondly, by activating pro-invasive gene expression. We have identified the AP-1 transcription factor fos-1 and the Notch homolog lin-12 as critical egl-43 targets. A positive feedback loop between fos-1 and egl-43 induces pro-invasive gene expression in the AC, while repression of lin-12 Notch expression by egl-43 ensures the G1 cell cycle arrest necessary for invasion. Reducing lin-12 levels in egl-43 depleted animals restored the G1 arrest, while hyperactivation of lin-12 signaling in the differentiated AC was sufficient to induce proliferation. Taken together, our data have identified egl-43 Evi1 as an important factor coordinating cell invasion with cell cycle arrest.

Published
2020

21. Physical and functional interaction between SET1/COMPASS complex component CFP-1 and a Sin3S HDAC complex in C. elegans

Author

Beurton, Flore, primary, Stempor, Przemyslaw, additional, Caron, Matthieu, additional, Appert, Alex, additional, Dong, Yan, additional, Chen, Ron A-j, additional, Cluet, David, additional, Couté, Yohann, additional, Herbette, Marion, additional, Huang, Ni, additional, Polveche, Hélène, additional, Spichty, Martin, additional, Bedet, Cécile, additional, Ahringer, Julie, additional, and Palladino, Francesca, additional

Published
2019
Full Text
View/download PDF

22. Accessible Region Conformation Capture (ARC-C) gives high-resolution insights into genome architecture and regulation

Author

Huang, Ni, Seow, Wei Qiang, Appert, Alex, Dong, Yan, Stempor, Przemyslaw, and Ahringer, Julie

Abstract

Nuclear organization and chromatin interactions are important for genome function, yet determining chromatin connections at high resolution remains a major challenge. To address this, we developed Accessible Region Conformation Capture (ARC-C), which profiles interactions between regulatory elements genome-wide without a capture step. Applied to Caenorhabditis elegans, ARC-C identifies approximately 15,000 significant interactions between regulatory elements at 500-bp resolution. Of 105 TFs or chromatin regulators tested, we find that the binding sites of 60 are enriched for interacting with each other, making them candidates for mediating interactions. These include cohesin and condensin II. Applying ARC-C to a mutant of transcription factor BLMP-1 detected changes in interactions between its targets. ARC-C simultaneously profiles domain-level architecture, and we observe that C. eleganschromatin domains defined by either active or repressive modifications form topologically associating domains (TADs) that interact with A/B (active/inactive) compartment-like structure. Furthermore, we discover that inactive compartment interactions are dependent on H3K9 methylation. ARC-C is a powerful new tool to interrogate genome architecture and regulatory interactions at high resolution.

Published
2022
Full Text
View/download PDF

23. Chromatin accessibility dynamics across C. elegans development and ageing

Author

Jänes, Jürgen, primary, Dong, Yan, additional, Schoof, Michael, additional, Serizay, Jacques, additional, Appert, Alex, additional, Cerrato, Chiara, additional, Woodbury, Carson, additional, Chen, Ron, additional, Gemma, Carolina, additional, Huang, Ni, additional, Kissiov, Djem, additional, Stempor, Przemyslaw, additional, Steward, Annette, additional, Zeiser, Eva, additional, Sauer, Sascha, additional, and Ahringer, Julie, additional

Published
2018
Full Text
View/download PDF

24. Author response: Chromatin accessibility dynamics across C. elegans development and ageing

Author

Jänes, Jürgen, primary, Dong, Yan, additional, Schoof, Michael, additional, Serizay, Jacques, additional, Appert, Alex, additional, Cerrato, Chiara, additional, Woodbury, Carson, additional, Chen, Ron, additional, Gemma, Carolina, additional, Huang, Ni, additional, Kissiov, Djem, additional, Stempor, Przemyslaw, additional, Steward, Annette, additional, Zeiser, Eva, additional, Sauer, Sascha, additional, and Ahringer, Julie, additional

Published
2018
Full Text
View/download PDF

25. Chromatin accessibility is dynamically regulated across C. elegans development and ageing

Author

Jänes, Jürgen, primary, Dong, Yan, additional, Schoof, Michael, additional, Serizay, Jacques, additional, Appert, Alex, additional, Cerrato, Chiara, additional, Woodbury, Carson, additional, Chen, Ron, additional, Gemma, Carolina, additional, Huang, Ni, additional, Kissiov, Djem, additional, Stempor, Przemysław, additional, Steward, Annette, additional, Zeiser, Eva, additional, Sauer, Sasha, additional, and Ahringer, Julie, additional

Published
2018
Full Text
View/download PDF

26. Correction: A team of heterochromatin factors collaborates with small RNA pathways to combat repetitive elements and germline stress

Author

McMurchy, Alicia N, primary, Stempor, Przemyslaw, additional, Gaarenstroom, Tessa, additional, Wysolmerski, Brian, additional, Dong, Yan, additional, Aussianikava, Darya, additional, Appert, Alex, additional, Huang, Ni, additional, Kolasinska-Zwierz, Paulina, additional, Sapetschnig, Alexandra, additional, Miska, Eric A, additional, and Ahringer, Julie, additional

Published
2017
Full Text
View/download PDF

27. A team of heterochromatin factors collaborates with small RNA pathways to combat repetitive elements and germline stress

Author

McMurchy, Alicia N, primary, Stempor, Przemyslaw, additional, Gaarenstroom, Tessa, additional, Wysolmerski, Brian, additional, Dong, Yan, additional, Aussianikava, Darya, additional, Appert, Alex, additional, Huang, Ni, additional, Kolasinska-Zwierz, Paulina, additional, Sapetschnig, Alexandra, additional, Miska, Eric A, additional, and Ahringer, Julie, additional

Published
2017
Full Text
View/download PDF

28. A team of heterochromatin factors collaborates with small RNA pathways to combat repetitive elements and germline stress

Author

McMurchy, Alicia N., primary, Stempor, Przemyslaw, additional, Gaarenstroom, Tessa, additional, Wysolmerski, Brian, additional, Dong, Yan, additional, Aussianikava, Darya, additional, Appert, Alex, additional, Huang, Ni, additional, Kolasinska-Zwierz, Paulina, additional, Sapetschnig, Alexandra, additional, Miska, Eric, additional, and Ahringer, Julie, additional

Published
2017
Full Text
View/download PDF

29. Author response: A team of heterochromatin factors collaborates with small RNA pathways to combat repetitive elements and germline stress

Author

McMurchy, Alicia N, primary, Stempor, Przemyslaw, additional, Gaarenstroom, Tessa, additional, Wysolmerski, Brian, additional, Dong, Yan, additional, Aussianikava, Darya, additional, Appert, Alex, additional, Huang, Ni, additional, Kolasinska-Zwierz, Paulina, additional, Sapetschnig, Alexandra, additional, Miska, Eric A, additional, and Ahringer, Julie, additional

Published
2017
Full Text
View/download PDF

30. Novel Roles of Caenorhabditis elegans Heterochromatin Protein HP1 and Linker Histone in the Regulation of Innate Immune Gene Expression

Author

Beurton, Flore, Stempor, Przemyslaw, Caron, Matthieu, Appert, Alex, Dong, Yan, Chen, Ron A-j, Cluet, David, Couté, Yohann, Herbette, Marion, Huang, Ni, Polvèche, Hélène, Spichty, Martin, Ahringer, Julie, Kozlowski, L., Robert, Valérie J., Mercier, Marine G., Janczarski, Stéphane, Merlet, Jorge, Garvis, Steve, Ciosk, Rafal, Meister, Peter, Xiao, Yu, Rohner, Sabine, Bodennec, Selena, Hudry, Bruno, Molin, Laurent, Solari, Florence, Gasser, Susan, Simonet, Thomas, Coustham, Vincent, Monier, Karine, Schott, Sonia, Karali, Marianthi, Studencka, M., Konzer, A., Moneron, G., Wenzel, D., Opitz, L., Salinas-Riester, G., Bedet, Cécile, Kruger, M., Hell, S., Wisniewski, J., Schmidt, H., Palladino, Francesca, Schulze, E., Jedrusik-Bode, M., Laboratoire de biologie et modélisation de la cellule (LBMC UMR 5239), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), The Gurdon Institute and Department of Genetics, University of Cambridge, Cambridge, UK, The Gurdon Institute, Department of Psychology, Renmin University of China, Etude de la dynamique des protéomes (EDyP), Laboratoire de Biologie à Grande Échelle (BGE - UMR S1038), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Department of Neurology, Johns Hopkins University (JHU), Reproduction et développement des plantes (RDP), École normale supérieure - Lyon (ENS Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Friedrich Miescher Institute for Biomedical Research (FMI), Novartis Research Foundation, Institute of Clinical Sciences, MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Recherches Avicoles (SRA), Institut National de la Recherche Agronomique (INRA), Laboratoire Joliot Curie, École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS), Telethon Institute for Genetics and Medicine, Telethon Institute, Max-Planck-Institut für Biophysikalische Chemie - Max Planck Institute for Biophysical Chemistry [Göttingen], Max-Planck-Gesellschaft, ESPCI ParisTech, FB Physik, Metallurgie und Werkstoffwissenschaften, Avt. Thermochemie une Mikrokinetik (TECH. UNIV. CLAUSTHAL), Clausthal University of Technology (TU Clausthal), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)

Subjects
Transcriptional Activation, Chromosomal Proteins, Non-Histone, Bacillus thuringiensis, Biology, Chromodomain, Histones, 03 medical and health sciences, Histone methylation, Histone H2A, Histone code, Animals, Protein Interaction Domains and Motifs, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Promoter Regions, Genetic, Molecular Biology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Histone binding, Genetics, 0303 health sciences, 030302 biochemistry & molecular biology, EZH2, Cell Biology, Articles, Immunity, Innate, 3. Good health, Gene Expression Regulation, Histone methyltransferase, Host-Pathogen Interactions, Heterochromatin protein 1, Protein Binding
Abstract

Linker histone (H1) and heterochromatin protein 1 (HP1) are essential components of heterochromatin which contribute to the transcriptional repression of genes. It has been shown that the methylation mark of vertebrate histone H1 is specifically recognized by the chromodomain of HP1. However, the exact biological role of linker histone binding to HP1 has not been determined. Here, we investigate the function of the Caenorhabditis elegans H1 variant HIS-24 and the HP1-like proteins HPL-1 and HPL-2 in the cooperative transcriptional regulation of immune-relevant genes. We provide the first evidence that HPL-1 interacts with HIS-24 monomethylated at lysine 14 (HIS-24K14me1) and associates in vivo with promoters of genes involved in antimicrobial response. We also report an increase in overall cellular levels and alterations in the distribution of HIS-24K14me1 after infection with pathogenic bacteria. HIS-24K14me1 localization changes from being mostly nuclear to both nuclear and cytoplasmic in the intestinal cells of infected animals. Our results highlight an antimicrobial role of HIS-24K14me1 and suggest a functional link between epigenetic regulation by an HP1/H1 complex and the innate immune system in C. elegans.

Published
2011
Full Text
View/download PDF

31. Comparative analysis of metazoan chromatin organization

Author

Ho, Joshua W. K., June, Youngsook L., Liu, Tao, Alver, Burak H., Lee, Soohyun, Ikegami, Kohta, Sohn, Kyung-Ah, Minoda, Aki, Tolstorukov, Michael Y., Appert, Alex, Parker, Stephen C. J., Gu, Tingting, Kundaje, Anshul, Riddle, Nicole C., Bishop, Eric, Egelhofer, Thea A., Hu, Sheng'en Shawn, Alekseyenko, Artyom A., Rechtsteiner, Andreas, Asker, Dalal, Belsky, Jason A., Bowmanm, Sarah K., Chens, Q. Brent, Chen, Ron A. -J., Day, Daniel S., Dong, Yan, Dose, Andrea C., Duan, Xikun, Epstein, Charles B., Ercan, Sevinc, Feingold, Elise A., Ferrari, Francesco, Garrigues, Jacob M., Gehlenborg, Nils, Good, Peter J., Haseley, Psalm, He, Daniel, Herrmann, Moritz, Hoffman, Michael M., Jeffers, Tess E., Kharchenko, Peter V., Kolasinska-Zwierz, Paulina, Kotwaliwale, Chitra V., Kumar, Nischay, Langley, Sasha A., Larschan, Erica N., Latorre, Isabel, Libbrecht, Maxwell W., Lin, Xueqiu, Park, Richard, Pazin, Michael J., Pham, Hoang N., Plachetka, Annette, Qin, Bo, Schwartz, Yuri B., Shoresh, Noam, Stempor, Przemyslaw, Vielle, Anne, Wang, Chengyang, Whittle, Christina M., Xue, Huiling, Kingstonm, Robert E., Kim, Ju Han, Bernstein, Bradley E., Dernburg, Abby F., Pirrotta, Vincenzo, Kuroda, Mitzi I., Noble, William S., Tullius, Thomas D., Kellis, Manolis, MacAlpine, David M., Strome, Susan, Elgin, Sarah C. R., Liu, Xiaole Shirley, Lieb, Jason D., Ahringer, Julie, Karpen, Gary H., Park, Peter J., Ho, Joshua W. K., June, Youngsook L., Liu, Tao, Alver, Burak H., Lee, Soohyun, Ikegami, Kohta, Sohn, Kyung-Ah, Minoda, Aki, Tolstorukov, Michael Y., Appert, Alex, Parker, Stephen C. J., Gu, Tingting, Kundaje, Anshul, Riddle, Nicole C., Bishop, Eric, Egelhofer, Thea A., Hu, Sheng'en Shawn, Alekseyenko, Artyom A., Rechtsteiner, Andreas, Asker, Dalal, Belsky, Jason A., Bowmanm, Sarah K., Chens, Q. Brent, Chen, Ron A. -J., Day, Daniel S., Dong, Yan, Dose, Andrea C., Duan, Xikun, Epstein, Charles B., Ercan, Sevinc, Feingold, Elise A., Ferrari, Francesco, Garrigues, Jacob M., Gehlenborg, Nils, Good, Peter J., Haseley, Psalm, He, Daniel, Herrmann, Moritz, Hoffman, Michael M., Jeffers, Tess E., Kharchenko, Peter V., Kolasinska-Zwierz, Paulina, Kotwaliwale, Chitra V., Kumar, Nischay, Langley, Sasha A., Larschan, Erica N., Latorre, Isabel, Libbrecht, Maxwell W., Lin, Xueqiu, Park, Richard, Pazin, Michael J., Pham, Hoang N., Plachetka, Annette, Qin, Bo, Schwartz, Yuri B., Shoresh, Noam, Stempor, Przemyslaw, Vielle, Anne, Wang, Chengyang, Whittle, Christina M., Xue, Huiling, Kingstonm, Robert E., Kim, Ju Han, Bernstein, Bradley E., Dernburg, Abby F., Pirrotta, Vincenzo, Kuroda, Mitzi I., Noble, William S., Tullius, Thomas D., Kellis, Manolis, MacAlpine, David M., Strome, Susan, Elgin, Sarah C. R., Liu, Xiaole Shirley, Lieb, Jason D., Ahringer, Julie, Karpen, Gary H., and Park, Peter J.

Abstract

Genome function is dynamically regulated in part by chromatin, which consists of the histones, non-histone proteins and RNA molecules that package DNA. Studies in Caenorhabditis elegans and Drosophila melanogaster have contributed substantially to our understanding of molecular mechanisms of genome function in humans, and have revealed conservation of chromatin components and mechanisms(1-3). Nevertheless, the three organisms have markedly different genome sizes, chromosome architecture and gene organization. On human and fly chromosomes, for example, pericentric heterochromatin flanks single centromeres, whereas worm chromosomes have dispersed heterochromatin-like regions enriched in the distal chromosomal 'arms', and centromeres distributed along their lengths(4,5). To systematically investigate chromatin organization and associated gene regulation across species, we generated and analysed a large collection of genome-wide chromatin data sets from cell lines and developmental stages in worm, fly and human. Here we present over 800 new data sets from our ENCODE and modENCODE consortia, bringing the total to over 1,400. Comparison of combinatorial patterns of histone modifications, nuclear lamina-associated domains, organization of large-scale topological domains, chromatin environment at promoters and enhancers, nucleosome positioning, and DNA replication patterns reveals many conserved features of chromatin organization among the three organisms. We also find notable differences in the composition and locations of repressive chromatin. These data sets and analyses provide a rich resource for comparative and species-specific investigations of chromatin composition, organization and function.

Published
2014
Full Text
View/download PDF

32. A20, ABIN-1/2, and CARD11 Mutations and Their Prognostic Value in Gastrointestinal Diffuse Large B-Cell Lymphoma

Author

Dong, Gehong, primary, Chanudet, Estelle, additional, Zeng, Naiyan, additional, Appert, Alex, additional, Chen, Yun-Wen, additional, Au, Wing-Yan, additional, Hamoudi, Rifat A., additional, Watkins, A. James, additional, Ye, Hongtao, additional, Liu, Hongxiang, additional, Gao, Zifen, additional, Chuang, Shih-Sung, additional, Srivastava, Gopesh, additional, and Du, Ming-Qing, additional

Published
2011
Full Text
View/download PDF

34. Chromatin accessibility dynamics across C. elegans development and ageing

Author

Jänes, Jürgen, Dong, Yan, Schoof, Michael, Serizay, Jacques, Appert, Alex, Cerrato, Chiara, Woodbury, Carson, Chen, Ron, Gemma, Carolina, Huang, Ni, Kissiov, Djem, Stempor, Przemyslaw, Steward, Annette, Zeiser, Eva, Sauer, Sascha, and Ahringer, Julie

Subjects
chromosomes, promoter, chromatin accessibility, C. elegans, gene expression, genomics, genetics, ATAC-seq, enhancer, 3. Good health, regulatory element
Abstract

An essential step for understanding the transcriptional circuits that control development and physiology is the global identification and characterization of regulatory elements. Here, we present the first map of regulatory elements across the development and ageing of an animal, identifying 42,245 elements accessible in at least one Caenorhabditis elegans stage. Based on nuclear transcription profiles, we define 15,714 protein-coding promoters and 19,231 putative enhancers, and find that both types of element can drive orientation-independent transcription. Additionally, more than 1000 promoters produce transcripts antisense to protein coding genes, suggesting involvement in a widespread regulatory mechanism. We find that the accessibility of most elements changes during development and/or ageing and that patterns of accessibility change are linked to specific developmental or physiological processes. The map and characterization of regulatory elements across C. elegans life provides a platform for understanding how transcription controls development and ageing., The work was supported by Wellcome Trust Senior Research Fellowships to JA (054523 and 101863), a Wellcome Trust PhD fellowship to JJ (097679), a Sir Robert Edwards Scholarship from Churchill College, an English Speaking Union Graduate Scholarship, and funding from the Cambridge Trust to MS, a Medical Research Council DTP studentship to JS, and a Thouron award to CW. This study was also supported by the European Sequencing and Genotyping Infrastructure (funded by the EC, FP7/2007-2013) under Grant Agreement 26205 (ESGI) as part of the transnational access program. We thank Drs. Hans Lehrach and Marie-Laure Yaspo for generous support of the ESGI project, Dr. Marc Sultan for setting up sequencing technology platforms, and Mathias Linser and the rest of the sequencing team of the Department of Vertebrate Genomics at the Max Planck Institute for Molecular Genetics for technical assistance. We also acknowledge core support from the Wellcome Trust (092096) and Cancer Research UK (C6946/A14492).

35. DREAM represses distinct targets by cooperating with different THAP domain proteins

Author

Gal, Csenge, Carelli, Francesco Nicola, Appert, Alex, Cerrato, Chiara, Huang, Ni, Dong, Yan, Murphy, Jane, Frapporti, Andrea, and Ahringer, Julie

Subjects
Cell Cycle Proteins, Retinoblastoma Protein, H3K9me2, retinoblastoma, Animals, Genetically Modified, Histones, THAP, transcriptional repression, Animals, quiescence, Protein Interaction Domains and Motifs, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Promoter Regions, Genetic, H2A.Z, DREAM, DNA Methylation, humanities, 3. Good health, E2F Transcription Factors, Gene Expression Regulation, lin-36, lin-15B, lin-35, psychological phenomena and processes, Protein Binding, Transcription Factors
Abstract

The DREAM (dimerization partner [DP], retinoblastoma [Rb]-like, E2F, and MuvB) complex controls cellular quiescence by repressing cell-cycle and other genes, but its mechanism of action is unclear. Here, we demonstrate that two C. elegans THAP domain proteins, LIN-15B and LIN-36, co-localize with DREAM and function by different mechanisms for repression of distinct sets of targets. LIN-36 represses classical cell-cycle targets by promoting DREAM binding and gene body enrichment of H2A.Z, and we find that DREAM subunit EFL-1/E2F is specific for LIN-36 targets. In contrast, LIN-15B represses germline-specific targets in the soma by facilitating H3K9me2 promoter marking. We further find that LIN-36 and LIN-15B differently regulate DREAM binding. In humans, THAP proteins have been implicated in cell-cycle regulation by poorly understood mechanisms. We propose that THAP domain proteins are key mediators of Rb/DREAM function.

Catalog

Books, media, physical & digital resources
See catalog results